In silico aquatic toxicity prediction of chemicals toward Daphnia magna and fathead minnow using Monte Carlo approaches

The fast-increasing use of chemicals led to large numbers of chemical compounds entering the aquatic environment, raising concerns about their potential effects on ecosystems. Therefore, assessment of the ecotoxicological features of organic compounds on aquatic organisms is very important. Daphnia magna and Fathead minnow are two aquatic species that are commonly tested as standard test organisms for aquatic risk assessment and are typically chosen as the biological model for the ecotoxicology investigations of chemical pollutants. Herein, global quantitative structure-toxicity relationship (QSTR) models have been developed to predict the toxicity (pEC(LC)50) of a large dataset comprising 2106 chemicals toward Daphnia magna and Fathead minnow. The optimal descriptor of correlation weights (DCWs) is calculated using the notation of simplified molecular input line entry system (SMILES) and is used to construct QSTR models. Three target functions, TF1, TF2, and TF3 are utilized to generate 12 QSTR models from four splits, and their statistical characteristics are also compared. The designed QSTR models are validated using both internal and external validation criteria and are found to be reliable, robust, and excellently predictive. Among the models, those generated using the TF3 demonstrate the best statistical quality with R2 values ranging from 0.9467 to 0.9607, Q2 values ranging from 0.9462 to 0.9603 and RMSE values ranging from 0.3764 to 0.4413 for the validation set. The applicability domain and the mechanistic interpretations of generated models were also discussed.